International Journal of Biological Macromolecules 43 (2008) 325–332 Contents lists available at ScienceDirect International Journal of Biological Macromolecules journal homepage: www.elsevier.com/locate/ijbiomac Photocrosslinkable starch-based polymers for ophthalmologic drug delivery A.P. Vieira a , P. Ferreira a,b , J.F.J. Coelho c , M.H. Gil a,∗ a Chemical Engineering Department, University of Coimbra, Pólo II, Rua Sílvio Lima, 3030-790 Coimbra, Portugal b Department of Health Sciences, Portuguese Catholic University, Estrada da Circunvalac ¸ ão, 3504-505 Viseu, Portugal c Centre of Ophthalmology, Biomedical Institute for Research in Light and Image (IBILI), Faculty of Medicine, University of Coimbra, 3000-354 Coimbra, Portugal article info Article history: Received 6 May 2008 Received in revised form 19 May 2008 Accepted 2 June 2008 Available online 6 June 2008 Keywords: Starch Drug delivery Photocrosslinking abstract This study focused on the development and characterization of a starch-based polymer with urethane link- ages to be used as a controlled drug delivery system for biomedical applications. Starch was modified with 2-isocyanatoethyl methacrylate in order to obtain a polymer containing carbon–carbon double bonds in its structure. This modified starch was then used to produce films by UV irradiation using Irgacure ® 2959 (CIBA) as the photoinitiator. The modified polymer was characterized by attenuated total reflectance- Fourier transform infrared (ATR-FTIR) spectroscopy. The swelling capacity, in artificial lachrymal fluid (performed both at room temperature and physiological temperature), and water contact angles mea- surements were determined. The in vitro biodegradation in artificial lachrymal fluid supplemented with lysozyme was also studied. Scanning electronic microscopy (SEM) was used to characterize the mor- phology of the materials immediately after synthesis and after biodegradation. Timolol maleate and sodium flurbiprofen were immobilized by adsorption and their in vitro release profiles were followed spectroscopically. © 2008 Elsevier B.V. All rights reserved. 1. Introduction Conventional ocular therapy for the treatment of acute and chronic diseases makes use of topical appliance of eye drops. This type of therapeutics represents nearly 90% of the marketed formu- lations. Still, this kind of appliance has a limited efficacy that is due to several factors. One of the major limiting factors for drug absorption from the lachrymal fluid into the anterior chamber, after eye drop administration, is the low permeability of the corneal epithelium that results in a very low (around 5%) drug absorp- tion by the cornea [1]. The remaining amount of drug flows with tears through the upper and lower canalicully into the nasolachry- mal ducts [2] and consequently may cause unwanted systemic side effects [3]. The self-protective mechanisms of the eye, such as rapid tear turnover, limit the absorption of the instilled drug in the eye [4]. In addition, application of ophthalmic drugs as drops results in a rapid variation in drug delivery rates to the cornea that limits the efficacy of therapeutic systems [5]. In order to improve the patient compliance for delivering the medications there is the need for finding some new implantable devices which could deliver the drugs in a long-lasting controlled ∗ Corresponding author at: Departamento de Engenharia Química, Universidade de Coimbra, Polo II, Pinhal de Marrocos, 3030-290 Coimbra, Portugal. Tel.: +351 239798743; fax: +351 239798703. E-mail address: hgil@eq.uc.pt (M.H. Gil). manner [6]. Using this strategy, the drug loss associated with sys- temic absorption would be minimized, and the resident time of the drug in the tear film increased [7]. An alternative approach to optimize ophthalmic drug delivery is the adaptation of bioadhesive systems [8], namely mucoadhesive ones, which have been proved to be successful in oral applications [9]. Bioadhesive delivery systems are designed to adhere to various tissue surfaces, mainly the mucosal epithelium, and can provide a localized delivery of an active agent to a specific site in the body such as the eye [3]. Some authors have come to the conclusion that mucoadhesion requires an expanded and hydrated polymer net- work [10]. In fact, according to Mulhbacher et al. [11] it is possible to describe three factors involved in the process of bioadhesion. The first is related to wetting and the swelling of the polymer, while the second concerns to the interpenetration of the polymeric chains with mucin. Finally, the third is related to the establishment of weak physical bonds between mucin and polymeric chains. These last interactions can be ionic, Van der Waals or hydrogen bonds and although they are, as said before, weak interactions individually, they can associate in a final strong adhesion phenomenon. Consid- ering this description, the most suitable polymers to be applied as mucoadhesive agents, will be hydrophilic macromolecules contain- ing numerous hydrogen bond forming groups [12]. Polysaccharides, being naturally occurring biomolecules, seem suitable compounds to develop this kind of systems, since they are well know as highly hydrophilic as well as biodegradable and biocompatible. In addi- tion, this kind of molecule can be modified to change its physical 0141-8130/$ – see front matter © 2008 Elsevier B.V. All rights reserved. doi:10.1016/j.ijbiomac.2008.06.002